CIP and SIP in Pharmaceuticals

What is difference between Clean-In-Place (CIP) and Sterilization-In-Place (SIP) Systems ?

CIP and SIP full form: Clean-In-Place (CIP) and Sterilization-In-Place (SIP) Systems respectively.

difference between Clean-In-Place (CIP) and Sterilization-In-Place (SIP) Systems

A. Cleaning in Place (CIP):

  • Cleaning in place (CIP), which uses detergents, is a technique that is increasingly widely used in the food and pharmaceutical industries. Accounts are provided by Kirkland (1986) and Hyde (1985).
  • CIP systems provide with a lot of benefits.
    • By cleaning more quickly, they reduce downtime, produce less effluent, and sometimes are less expensive.  
    • They reduce manual labour and the associated safety and health issues.
    • Particularly minimised are the risks associated with vessel entry and slick terrain.
  • CIP systems are available as mobile systems that can be utilized on many units as well as systems devoted to specific units.
  • They can be controlled manually or automatically using a set of instructions.
  • Open or closed equipment can both be cleaned. Kirkland explains the usage of a computer-generated spray ball for open equipment that is specific to the vessel.
  • A typical CIP sequence is:
    1. Water pre-rinse, to eliminate gross material;
    2. Detergent circulation, to eliminate debris and scale;
    3. Intermediate water rinse, to eliminate detergent;
    4. Sterile circulation, to terminate residual organisms; and
    5. Final water rinse, to remove CIP solutions.
  • There are numerous methods for recovering water and reducing the amount of solutions utilised.

Benefits of CIP:

As CIP systems are intended to integrate with processing equipment, they deliver a number of advantages to processing operations.

1. Increased Product Safety

  • By automating cleaning, CIP reduces the likelihood of human error, which might result in a product that is dangerous.
  • Through CIP and monitoring sensors, contamination hazards are reduced.

2. Increased Employee Safety

  • CIP decreases worker chemical interaction by containing cleaning solutions within the system.
  • No Vessel Entry – Workers don’t have to go into tanks to clean.

B. Sterilization-In-Place (SIP)

  • The term “sterilization-in-place” (SIP) refers to the in-situ sterilization of a system or piece of processing machinery.
  • SIP is designed to decrease post-sterilization handling, including that required to make aseptic connections, to a minimum or eliminate it altogether.
  • Once disinfected in this way, mobile process equipment (such as portable tanks, storage vessels, and other equipment) may be moved.
  • Any of the physical techniques listed below—moist heat, dry heat, gas, liquid, or vapour (explained below)—can be used to carry out the SIP process.

Sterilization-In-Place (SIP) Methods:

Moist Heat:

  1. The most used technique for SIP of big systems is saturated steam.
  2. Most installations employ gravity displacement cycles that were initially created for steam sterilisers (the size and complexity of many systems preclude the use of pre-vacuum cycles).
  3. The provision for air removal, condensate discharge, and steam removal post-dwell are among the crucial factors.
  4. 3, 4 This approach is frequently utilised for big systems such as bioreactors, sterile bulk manufacturing, storage tanks and distribution lines.

Superheated Water:

  1. Systems used for Water for Injection (WFI) and Purified Water could be sterilized by use of superheated water (water that is being heated above its boiling point and pressurized to maintain it as a liquid phase) circulating through the system.
  2. This method has the capability to sterilize vessels, filters, and other moistened components at a similar time.
  3. Elimination of residual water following to the sterilization phase is recommended.

Dry Heat:

  1. For SIP of spray dryers and the material collection systems connected to them, dry heat has been employed. These systems use HEPA filters to provide the air supply for sterilizing.


  1. Sterilization-In-Place (SIP) as Gas-phase has been used for non- and low-pressure-rated process equipment, such as pre-freezers, freeze dryers, process vessels, and other equipment.


  • Liquid chemical sterilization is best suitable for liquid-handling systems and can be used only for fully wetted surfaces.
  • This process is similar to those using superheated water except the lethal modality is chemical rather than thermal.


  • Sterilizing vapors have been used for the in-situ (situated in the original place) sterilization of the same types of process equipment as those treated with sterilizing gases.

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